Chronic Obstructive Pulmonary Disease (COPD) is a major cause of outpatient medical care, hospital admission days and mortality (Vestbo, J., et al. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease, GOLD Executive Summary. Am J Respir Crit Care Med (2012)). Acute episodes of worsening COPD are characterized by cough, sputum production, shortness of breath and wheezing (often referred to as acute exacerbations of COPD or AECOPD) and are treated with antibiotics and/or prednisone. Although the major risk factor for COPD is a history of smoking, most current and former smokers do not have COPD. Furthermore, smokers without COPD have acute episodes of airway disease clinically identical to exacerbations of COPD (often referred to as acute bronchitis).
Recent work suggests that there are subsets of current and former smokers who are more susceptible to frequent episodes of chronic bronchitis or acute exacerbations of COPD (Hurst, J. R., et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 363, 1128-1138 (2010)). Clinical predictors for these episodes include: previous episodes of bronchitis or exacerbations of COPD, airflow obstruction on spirometry, low respiratory health scores, and gastroesophageal reflux (Hurst, J. R., et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 363, 1128-1138 (2010)). These susceptible patients are also postulated to be more prone to systemic inflammation. Evidence for systemic inflammation from previous large studies includes: elevated white blood cell count and fibrinogen (Thomsen, M., et al. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. Jama 309, 2353-2361 (2013)), and C reactive Protein (CRP). These studies did not include at risk current and former smokers and were limited to the study of a small number of biomarkers. Other studies have suggested biomarkers such as surfactant protein D (Ozyurek, B A., et al. Multidisciplinary respiratory medicine, 2013; 8:36), fetuin A (Minas, M., et al., COPD 2013, 10:28-34, adiponectin and CRP (Kirdar, S., et al. Scandinavian Journal of Clinical and Laboratory Investigation, 2009; 69: 219-224) might be predictive of AECOPDs. These studies have been limited by small sample size and limited clinical phenotyping with incomplete adjustment for covariates predictive of exacerbations.
The presence of emphysema has been associated with increased mortality and increased risk of lung cancer in COPD. Similarly, the distribution of emphysema is important for determining patients eligible for lung volume reduction procedures. High resolution computed tomography (HRCT) chest scans are useful in characterizing the distribution of emphysema and providing quantitative measurements, however they are expensive, may require a separate patient visit and raise concerns about radiation exposure.
At present, there exists a need for development of reliable and sensitive molecular markers which can be used to predict subjects who are susceptible to exacerbation of COPD as well as the presence or absence of emphysema.